Acetamide → N2,N2-Dimethyl-6-nitro-2,5-indanediamine

Temperature

20 °C

A solution of cHNO3 (70%, 13.4 mL, 211 mmol) in TFA (15 mL) was added dropwise to a stirred solution of acetamide 109 (15.38 g, 70.5 mmol) in TFA (120 mL) and the solution stirred at 20° C. for 16 h. The solution was poured into ice/water (1.2 L) and the pH adjusted to 10 with cNH3. The mixture was extracted with DCM (4×150 mL), the combined organic fraction dried and the solvent evaporated. The residue was filtered through a short column of silica, eluting with a gradient (0-15%) of MeOH/DCM, to give a 6:1 mixture of N-[2-(dimethylamino)-6-nitro-2,3-dihydro-1H-inden-5-yl]acetamide and N-[2-(dimethylamino)-4-nitro-2,3-dihydro-1H-inden-5-yl]acetamide (16.7 g, 90%). A solution of the acetamide mixture (16.7 g, 63.4 mmol) in EtOH (300 mL) and cHCl (70 mL) was stirred at reflux temperature for 4 h. The mixture was cooled and the EtOH evaporated. The mixture was diluted with water (200 mL) and the pH adjusted to 9 with cNH3. The precipitate was filtered, washed with water (40 mL), dried and recrystallised from EtOAc/pet. ether to give pure 6-nitroaniline 110 (8.12 g, 52%) as a red solid: mp 19-121° C.; 1H NMR δ 7.91 (s, 1H, H-7), 6.61 (s, 1H, H-4), 6.00 (br s, 2H, NH2), 2.95-3.06 (m, 3H, H-2, CH2), 2.74-2.84 (m, 2H, CH2), 2.29 [s, 6H, N(CH3)2]; 13C NMR δ 151.8, 144.4, 131.6, 131.4, 121.0, 113.6, 67.8, 43.8 (2), 37.9, 36.2. Anal. calcd for C11H15N3O2: C, 59.7; H, 6.8; N, 19.0. Found: C, 59.5; H, 6.9; N, 18.9%.

1. extractionThe mixture was extracted with DCM (4×150 mL)
2. customthe combined organic fraction dried
3. customthe solvent evaporated
4. filtrationThe residue was filtered through a short column of silica
5. washeluting with a gradient (0-15%) of MeOH/DCM
6. customto give
7. temperatureat reflux temperature for 4 h
8. temperatureThe mixture was cooled
9. customthe EtOH evaporated
10. additionThe mixture was diluted with water (200 mL)
11. filtrationThe precipitate was filtered
12. washwashed with water (40 mL)
13. customdried
14. customrecrystallised from EtOAc/pet. ether

ORD record

ord-0def585cd47e492b96cb7ffce75daf48

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989451B2